The aim of this project is to study carbohydrate structures in mucins and relate these to states of differentiation and malignant transformation in colonic epithelium. One arm of the study is designed to detect and develop markers of cellular differentiation, malignancy and premalignant tissue. A second arm is designed to study the structural and enzymatic basis of the heterogeneity of colonic mucins. Differentiation-dependent changes have been found in the normal colon; transformation-associated changes have been found in cancer and "transitional mucosa." Identification of modifications in mucin structure have been found in a variety of premalignant epithelia, including adenomatous polyps, rectal biopsies from patients with chronic ulcerative colitis, and colons from mice treated with a chemical carcinogen. Preliminary evidence suggests that cancer-associated alterations in colonic mucins may be due to incomplete glycosylation of the oligosaccharide chains.